Cancer chemotherapy drugs which bind to DNA will be investigated with respect to their mode of interaction with DNA and the conditions which affect their binding. Synchronized tissue culture cells will be used to determine whether there are periods during the cell cycle when DNA is particularly susceptible to drug binding. Attempts will be made to determine whether there are any differences between RNA and DNA inhibitors in the time of maximum binding to DNA. More precise knowledge of the nature of binding will be investigated by studying the interaction of drugs with DNA of various cell structures and of various cell fractions. These studies will contribute toward understanding the mechanism of action of a large class of drugs which have shown activity in treatment of cancer in man and may provide information which may be useful in the formulation of drug schedules for cancer patients and in the design of more effective cancer chemotherapy agents.